Daniel P. Kiehart

Professor of Biology

Office: 
4330 French Family Science Center, Science Drive, Duke University, Durham, NC 27708-0338
Campus Box: 
Box 90338, Dept. Biology, Duke University, Durham, NC 27708-1000
Phone: 
(919) 613-8157
Our intellectual focus is on identifying determinants of cell shape that function during development. Utilizing molecular genetic and reverse genetic approaches in Drosophila, we have shown that conventional nonmuscle myosin is necessary for driving both cell division and post-mitotic cell shape changes for morphogenesis, and cellular locomotions. Currently, we are investigating how myosin elicits cell shape change and how its function is regulated through filament formation, phosphorylation, sub-cellular targeting and small GTP-binding protein function. We are characterizing myosin light chain kinase; a novel myosin VII heavy chain; and additional elements that participate in localizing myosin and transmitting the forces that it produces. We used screens for aberrant cell shape induced in the yeast S. pombe by expression of transfected Drosophila cDNAs. These experiments show that elements that define cell shape are conserved throughout phylogeny and that a screen in yeast is a valuable tool for recovering heterologous cDNAs that encode cytoskeletal elements and the proteins that regulate them. In fly, we are identifying gene products that are necessary for myosin function by genetically recovering second site non-complementing loci and biochemically recovering proteins that bind to myosin. To date, our experiments identify ~30 loci that genetically interact with myosin and a kinase activity that phosphorylates myosin heavy chain and establish genetically, that the Rho signalling pathway is required in concert with nonmuscle myosin II for morphogenesis. We are also using manipulation studies to understand the forces that drive cellularization and morphogenesis. We show that both the amnioserosa and the leading edge of the lateral epidermis contribute to the movements of dorsal closure. Finally, we are examining the role these proteins play in movements that occur during wound healing.

Education

  • Ph.D., University of Pennsylvania 1979

  • B.A., University of Pennsylvania 1973

Lu, H, Sokolow, A, Kiehart, DP, and Edwards, GS. "Quantifying dorsal closure in three dimensions." Molecular biology of the cell 27, no. 25 (December 2016): 3948-3955. Full Text

Marston, DJ, Higgins, CD, Peters, KA, Cupp, TD, Dickinson, DJ, Pani, AM, Moore, RP, Cox, AH, Kiehart, DP, and Goldstein, B. "MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation." Current biology : CB 26, no. 16 (August 2016): 2079-2089. Full Text

Lu, H, Sokolow, A, Kiehart, DP, and Edwards, GS. "Remodeling Tissue Interfaces and the Thermodynamics of Zipping during Dorsal Closure in Drosophila." Biophysical journal 109, no. 11 (December 2015): 2406-2417. Full Text

Goldstein, B, and Kiehart, DP. "Moving Inward: Establishing the Mammalian Inner Cell Mass." Developmental cell 34, no. 4 (August 2015): 385-386. Full Text

Kiehart, DP. "Epithelial morphogenesis: apoptotic forces drive cell shape changes." Developmental cell 32, no. 5 (March 2015): 532-533. Full Text

Wells, AR, Zou, RS, Tulu, US, Sokolow, AC, Crawford, JM, Edwards, GS, and Kiehart, DP. "Complete canthi removal reveals that forces from the amnioserosa alone are sufficient to drive dorsal closure in Drosophila." Molecular biology of the cell 25, no. 22 (November 2014): 3552-3568. Full Text

Chen, B-C, Legant, WR, Wang, K, Shao, L, Milkie, DE, Davidson, MW, Janetopoulos, C, Wu, XS, Hammer, JA, Liu, Z, English, BP, Mimori-Kiyosue, Y, Romero, DP, Ritter, AT, Lippincott-Schwartz, J, Fritz-Laylin, L, Mullins, RD, Mitchell, DM, Bembenek, JN, Reymann, A-C, Böhme, R, Grill, SW, Wang, JT, Seydoux, G, Tulu, US, Kiehart, DP, and Betzig, E. "Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution." Science (New York, N.Y.) 346, no. 6208 (October 23, 2014): 1257998-. Full Text

Hunter, GL, Crawford, JM, Genkins, JZ, and Kiehart, DP. "Ion channels contribute to the regulation of cell sheet forces during Drosophila dorsal closure." Development 141, no. 2 (January 2014): 325-334. Full Text

Tulu, US, Beckerle, MC, and Kiehart, DP. "Cell Junctions and the Tension Sensitive, Supracellular Purse Strings in Drosophila Dorsal Closure (Submitted)." J. Cell Biol. (June 2012). (Academic Article)

Hunter, G, Crawford, J, Genkins, J, and Kiehart, DP. "Ion channels function in the mechanoregulation of cell sheet forces during Drosophila morphogenesis (Submitted)." Developmental Cell (May 2012). (Academic Article)

Pages

Genetics Training Grant awarded by National Institutes of Health (Mentor). 1979 to 2020

Organization and Function of Cellular Structure awarded by National Institutes of Health (Mentor). 1975 to 2020

Morphogenesis: Biophysics and Genetics of Dorsal Closure awarded by National Institutes of Health (Principal Investigator). 1984 to 2018

Training Program in Developmental and Stem Cell Biology awarded by National Institutes of Health (Mentor). 2001 to 2017

Lightsheet Imaging System awarded by National Institutes of Health (Major User). 2016 to 2017

Structural Biology and Biophysics Training Program awarded by National Institutes of Health (Mentor). 1994 to 2015

Institutional Training Grant in Pediatric Cardiology awarded by National Institutes of Health (Faculty Member). 2009 to 2015

Design and Implementation of Genetically Encoded Myosin Based Force Sensors awarded by National Institutes of Health (Principal Investigator). 2012 to 2015

New Console and Cold Probe for the Duke 600 MHz NMR Spectrometer System awarded by National Institutes of Health (Major User). 2013 to 2014

Non Muscle Myosin II Contractility Putatively Regulates Scar Contracture awarded by National Institutes of Health (Co-Mentor). 2008 to 2013

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